Genetic Variant NM_001242809.2:c.472C>G (chr6-89612326-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001242809.2(ANKRD6):c.472C>G(p.Arg158Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,413,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.63

Publications

0 publications found

Variant links:

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD6 links:

LYRM2 (HGNC:25229): (LYR motif containing 2)

LYRM2 links:

LOC124901359 (HGNC:):

LOC124901359 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.841

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD6	NM_001242809.2	MANE Select	c.472C>G	p.Arg158Gly	missense	Exon 6 of 16	NP_001229738.1	Q9Y2G4-2
ANKRD6	NM_001242811.1		c.472C>G	p.Arg158Gly	missense	Exon 6 of 16	NP_001229740.1	Q9Y2G4-2
ANKRD6	NM_014942.4		c.472C>G	p.Arg158Gly	missense	Exon 6 of 16	NP_055757.3	Q9Y2G4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.472C>G	p.Arg158Gly	missense	Exon 6 of 16	ENSP00000345767.4	Q9Y2G4-2
ANKRD6	ENST00000447838.6	TSL:1	c.472C>G	p.Arg158Gly	missense	Exon 6 of 16	ENSP00000396771.2	Q9Y2G4-3
ANKRD6	ENST00000369408.9	TSL:1	c.472C>G	p.Arg158Gly	missense	Exon 6 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413804

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698576

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32304

American (AMR)

AF:

0.00

AC:

AN:

37748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25294

East Asian (EAS)

AF:

0.00

AC:

AN:

37076

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086710

Other (OTH)

AF:

0.00

AC:

AN:

58654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.0085

MutationAssessor

Benign

1.5

PhyloP100

5.6

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.4

REVEL

Uncertain

0.46

Sift

Benign

0.060

Sift4G

Uncertain

0.053

Polyphen

1.0

Vest4

0.78

MutPred

0.55

Gain of catalytic residue at V159 (P = 0.0225)

MVP

0.87

MPC

0.37

ClinPred

0.99

GERP RS

5.6

Varity_R

0.40

gMVP

0.47

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over